College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana, United States.
Int J Pharm Compd. 2021 Mar-Apr;25(2):169-175.
Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.
甲硝唑适用于治疗滴虫病、阿米巴病和厌氧细菌感染。甲硝唑的剂量方案在治疗滴虫病、肝功能损害患者以及儿科和老年患者时需要个体化。对甲硝唑治疗用途的回顾表明，需要灵活调整剂量。这种灵活性可以通过口服液体制剂轻松实现。然而，目前市场上没有甲硝唑的商业液体制剂。甲硝唑仅以 250 毫克和 500 毫克薄膜包衣片剂的形式供应。从纯药物粉末或商业片剂临时配制的混悬剂将为满足患者的独特需求提供一种方便的选择。本研究旨在确定 PCCA SuspendIt 中甲硝唑临时配制混悬剂的物理化学和微生物稳定性。这种基质是一种无糖、无对羟基苯甲酸酯、无染料、无麸质的触变载体，含有一种从罗汉果中提取的天然甜味剂。研究设计包括两个甲硝唑浓度，以提供在最终由药剂师配制时使用的有间隔浓度范围内的稳定性文件。开发并验证了一种用于测定 PCCA SuspendIt 中甲硝唑化学稳定性的稳健的稳定性指示超高效液相色谱分析方法。甲硝唑混悬剂以 25 毫克/毫升和 50 毫克/毫升的浓度在 PCCA SuspendIt 中制备，选择的浓度范围代表了药物常用剂量范围。样品储存在 5°C 和 25°C 两种温度条件下的塑料琥珀色处方瓶中。样品在以下时间点（天）进行初始和后续检测：7、14、28、42、59、90、122 和 180。还记录了 pH 值、粘度和外观等物理数据。还测试了微生物稳定性。所有测量均重复三次。稳定的临时产品定义为在整个采样期间保留至少 90%初始药物浓度且免受微生物生长影响的产品。研究表明，在研究的两种温度下，甲硝唑浓度均未降至标签声称（初始药物浓度）的 97%以下。未观察到微生物生长。粘度和 pH 值也没有显著变化。这项研究表明，甲硝唑在 PCCA SuspendIt 中在冰箱和室温下 180 天内物理上、化学上和微生物上均稳定，从而为甲硝唑提供了一种可行的、配制的液体制剂替代方案，并延长了超过使用期限以满足患者的需求。
